These results suggest that lncARSR acts as an oncogene in NSCLC development and could serve as a new potential therapeutic target. AJTR Copyright © 2020.Lung cancer ranks as the most common cancer and leading cause of cancer-related deaths worldwide. Of all lung cancer types, non-small cell lung cancer (NSCLC) accounts for 85 percent of all cases. The high mortality of NSCLC occurs mainly because of poor prognosis in patients with recurrent and metastatic cancer. Cisplatin-containing chemotherapy is the first option to treat recurrent and metastatic NSCLC. Additionally, targeted therapy plays an important role to prolong life in patients. Currently, EGFR inhibitors are the most important targeted anti-cancer drugs for patients with EGFR mutations in the clinical setting. Another important kinase inhibitor for targeted therapy is the MEK inhibitor, Trametinib, which is often used for patients with BRAF mutation or MEK/ERK activation in the tumors. In this study, we determined whether a combination of the pan-ErbB kinase inhibitor, Afatinib, and MEK inhibitor, Trametinib, could more effectively inhibit NSCLC cell proliferation when compared to either single treatment. We found that Afatinib inhibited phosphorylation of EGFR, HER2, HER3, and HER4, as well as Akt, whereas it elevated ERK phosphorylation. Conversely, Trametinib treatment led to ERK inhibition, but induced Akt phosphorylation. However, the combination of Afatinib and Trametinib inhibited all of the above-mentioned signaling pathways and synergistically suppressed cell proliferation. Our data indicate that co-targeting of ErbB family and MEK/ERK pathways through a combination of Afatinib and Trametinib could be a potential effective strategy to treat NSCLC. AJTR Copyright © 2020.L1-cell adhesion molecule (L1CAM, L1) belongs to the immunoglobulin superfamily and was originally found to play a role in nerve cells. Recently, the expression and prognostic value of L1 has been established in several cancers, including colorectal cancer (CRC). However, its association with lymph node metastasis in CRC and the mechanisms underlying its effects remain unclear. In this study, we evaluated the L1 transcript levels in CRC (n=12) and normal intestinal tissues (n=15) by qRT-PCR. Western blotting was used to evaluate L1 and pERK1/2 expression levels. Immunohistochemistry was performed to evaluate the relationship between L1 and pERK1/2 in CRC tissues with different levels of differentiation. The mRNA expression levels in CRC tissues were significantly higher compared to normal intestinal tissues. Western blotting demonstrated that both L1 and pERK1/2 levels were higher in CRC than in normal tissues. Immunohistochemistry confirmed that L1 and pERK1/2 levels in adenomas with lymph node metastasis were significantly higher than in poorly and well-differentiated adenomas, indicating that L1 and pERK1/2 levels correlated with CRC lymph node metastasis. In conclusion, L1 and pERK1/2 were significantly up-regulated in CRC tissues and lymph node metastasis may occur via the L1CAM-mediated ERK pathway in CRC. AJTR Copyright © 2020.Currently, the acquired resistance of the hepatocellular carcinoma (HCC) first-line therapeutic agent-sorafenib (SOR) remains a major challenge for HCC management. Recent evidence suggested the association between CXCL/CXCRs chemokines and chemotherapy resistant in cancer cells. Hence, exploring the internal mechanism of CXCRs involved in SOR resistance will help to improve the efficacy of HCC. SOR-resistant HCC cells (Huh7-SOR) were established through escalating concentration of SOR. Glucose consumption, lactate production, intracellular ATP levels and oxygen consumption of HCC cells were determined by using the associated detected kits. Effects of CXCR3 on metabolic phenotype of HCC cells, AMPK pathway activity and adipocytokines were demonstrated by knocking down CXCR3 expression with the CXCR3 siRNA technique combined with qPCR and western blot. During the indicated procedure, SOR-resistant HCC cells-Huh7-SOR presented EMT-like morphologic change and underwent glycolysis to OXPHOS switch, representing reduced glucose consumption and lactate production, but increased oxygen consumption level and intercellular ATP levels. Moreover, metabolic alteration in SOR-resistance HCC cells was mediated by CXCR3. Mechanistically, CXCR3 induced metabolic alteration in SOR-resistance HCC cells through downregulating AMPK pathway activity and lipid peroxidation as well as upregulating levels of adipocytokines. The activation of A MPK pathway with metformin achieved the sensitization of HCC to SOR treatment in vivo. These findings unravel the association between metabolic alteration and SOR-resistance in HCC cells and demonstrate an important role of CXCR3 in the development of HCC cells resistance to SOR treatment and a novel mechanism of CXCR3 regulating AMPK pathway activity and adipocytokine signaling, lipid peroxidation resulted in metabolic alteration during the chemoresistance. AJTR Copyright © 2020.Fragile X syndrome (FXS) is one of the most common forms of inherited mental retardation; it is usually associated with the transcriptional silencing of the Fmr1 gene and loss of its encoded protein, the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein and participates in regulating the development of dendritic spines and synaptic plasticity. To uncover the possible role of microRNAs (miRNAs) in FXS and their relationship with FMRP, we used microarray analysis to investigate the miRNA expression profiles in the hippocampal tissues of Fmr1 knockout (Fmr1-KO) mice and wild type (WT) mice. A total of 75 differentially expressed miRNAs were identified, of which 58 were significantly upregulated and no miRNAs were significantly downregulated in Fmr1-KO mice.  https://www.selleckchem.com/products/mitomycin-c.html  Quantitative real-time PCR (qRT-PCR) analysis was applied to validate the expression of 7 upregulated miRNAs; results indicated that the levels of only miR-449a and miR-720 were significantly upregulated. We further used bioinformatics software and databases to predict the target genes of these two miRNAs. The genes were related to dendritic spine development and synaptic plasticity; the qRT-PCR and western blotting results showed that cyclin-dependent kinase 5 (CDK5) and synaptotagmin 1 (SYT1) were differentially expressed in the Fmr1-KO mice and WT mice. In conclusion, this study evidenced diverse changes in the expression of miRNAs, and validated the miRNAs and their targeted genes in Fmr1-KO mice. Although further studies are required to better understand the function of miRNAs in FXS, the present research highlights a potential role of miRNAs in the pathogenesis of FXS. AJTR Copyright © 2020.